Scientists discover an additional function for the peroxisome protein Pex11p

New study in PNAS shows membrane remodelling protein Peroxin 11 (Pex11p) plays a role in peroxisomal fission. Organelle fission is crucial for human health and development as it regulates the number of peroxisomes inside the cells.

Peroxisomes are cytoplasmic organelles which contain various enzymes responsible for vital reactions, such as lipid metabolism. Drs. Michael Schrader and Joe Costello from the University of Exeter have collaborated with scientists from the University of Groningen, The Netherlands to reveal the molecular mechanisms of the peroxisome division machinery across species. This partnership is part of the European Marie Curie Initial Training Network PERFUME (PERoxisome formation, FUnction, and MEtabolism).

Recently, they have published in PNAS the results of their work: the membrane remodelling protein Peroxin 11 (Pex11p), that was previously known to take part in the elongation of the peroxisomal membrane prior to division, also plays a critical role in the final peroxisomal fission step, it is therefore regulating the number of peroxisomes per cell. They demonstrated that, in mammalian cells, Pex11 physically interacts with the Dynamin-Like-Protein DLP1, leading to its activation. DLP1 is a mechanochemical enzyme which forms ring-like structures around membranes to cleave them. This mechanism has also been shown in yeast by their collaborators, proving it is conserved across species and represents the first report of a requirement for an activator protein in dynamin-like protein function.

This newly reported function of Pex11p is of great interest for the scientific community since the peroxisome is a crucial subcellular compartment for lipid metabolism and protection against oxidative stress. Loss of peroxisomal function is the cause of several human diseases, including neurodegenerative disorders, developmental defects, and age-related pathologies.

When asked about the significance of this research, Dr. Michael Schrader, Associate Professor in Cell Biology in Biosciences said, “The Pex11 proteins combine many fascinating properties across species and are key to the regulation of peroxisome proliferation. As elevated peroxisome numbers can be beneficial for cell performance and viability, the understanding of Pex11 function opens therapeutic pathways for the modulation of organelle number and activity.”